This is a new RO1 grant application to study the evolutionary diversification of the human blood fluke, Schistosoma mansoni, and its snail host, Biomphalaria spp. Schistosomiasis is one of the most serious of parasitic diseases, and future control efforts will require a better understanding of the basic biology of these parasites, including their evolutionary biology. Moreover an important key to understanding schistosome evolution is to comprehend their dependence on snails as intermediate hosts, yet there exists a lack of even rudimentary knowledge of the evolutionary relationships among these snail vectors, and how those relationships might influence schistosome evolution. However, in order to obtain a 'global' perspective on past and present evolution of S. mansoni and its snail host species, representative samples across the entire geographic range of these organisms would be required for a comprehensive analysis. Accordingly, the PI proposes to obtain samples of S. mansoni populations and corresponding host snails covering their geographic ranges, and, using genomic and mitochondrial target gene sequence analyses in conjunction with powerful molecular phylogenetic techniques, he will then construct a series of cladograms or trees to develop robust hypotheses regarding evolutionary relationships among S. mansoni populations, and among their snail hosts. The data generated will address questions of how genetic variation in S. mansoni is apportioned among and within continents, whether this variation results from geographic isolation or is driven by coevolution with their hosts, and what factors influence variability within parasite populations. Hypotheses also will be provided regarding the origins of Biomphalaria, whether susceptibility is an ancestral or derived trait, how Biomphalaria is related to other snail host genera, and how snail evolution may have influenced schistosome evolution.